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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model.
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Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model.

机译：在鼠模型中所选结核分枝杆菌菌株的毒力，免疫病理学和可传播性。

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After encounter with Mycobacterium tuberculosis, a series of non-uniform immune responses are triggered that define the course of the infection. Eight M. tuberculosis strains were selected from a prospective population-based study of pulmonary tuberculosis patients (1995-2003) based on relevant clinical/epidemiological patterns and tested in a well-characterized BALB/c mouse model of progressive pulmonary tuberculosis. In addition, a new mouse model of transmissibility consisting of prolonged cohousing (up to 60 days) of infected and naive animals was tested. Four phenotypes were defined based on strain virulence (mouse survival, lung bacillary load and tissue damage), immunology response (cytokine expression determined by real-time polymerase chain reaction) and transmissibility (lung bacillary loads and cutaneous delayed-type hypersensitivity in naive animals).We identified four clearly defined strain phenotypes: (1) hypervirulent strain with non-protective immune response and highly transmissible; (2) virulent strain, associated with high expression of proinflammatory cytokines (tumour necrosis factor and interferon) and very low anti-inflammatory cytokine expression (interleukins 4 and 10), which induced accelerated death by immunopathology; (3) strain inducing efficient protective immunity with lower virulence, and (4) strain demonstrating strong and early macrophage activation (innate immunity) with delayed participation of acquired immunity (interferon expression). We were able to correlate virulent and transmissible phenotypes in the mouse model and markers of community transmission such as tuberculin reactivity among contacts, rapid progression to disease and cluster status. However, we were not able to find correlation with the other two phenotypes. Our new transmission model supported the hypothesis that among these strains increased virulence was linked to increased transmission.
机译：遇到结核分枝杆菌后，会触发一系列不均匀的免疫反应，从而确定感染的过程。根据相关的临床/流行病学模式，从一项基于人群的前瞻性肺结核患者研究（1995-2003年）中选择了八株结核分枝杆菌菌株，并在进行性肺结核的特征明确的BALB / c小鼠模型中进行了测试。此外，还测试了一种新的可传播性小鼠模型，该模型由受感染和天真的动物的长期饲养（长达60天）组成。根据毒株毒力（小鼠存活率，肺细菌负荷和组织损伤），免疫学应答（通过实时聚合酶链反应确定的细胞因子表达）和传播性（幼稚动物的肺细菌负荷和皮肤迟发型超敏反应）定义了四种表型。我们确定了四种明确定义的菌株表型：（1）具有非保护性免疫反应且高度可传播的高毒力菌株; （2）强毒株，与促炎细胞因子（肿瘤坏死因子和干扰素）的高表达和极低的抗炎细胞因子的表达（白介素4和10）有关，它们通过免疫病理学诱导加速死亡。 （3）菌株诱导出具有较低毒力的有效保护性免疫，以及（4）菌株显示了强而早期的巨噬细胞激活（先天免疫），而后天获得性免疫（干扰素表达）的参与延迟。我们能够关联小鼠模型中的强毒和可传播表型，以及社区传播的标志物，例如接触者之间的结核菌素反应性，疾病的快速进展和集群状态。但是，我们无法找到与其他两个表型的相关性。我们的新传播模型支持以下假设：在这些菌株中，毒力增加与传播增加有关。

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